1. Therapeutic impact of cytoreductive surgery and irradiation of posterior fossa ependymoma in the molecular era: A retrospective multicohort analysis
- Author
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Uri Tabori, Marta M. Alonso, Frank S. Lieberman, James T. Rutka, Xing Fan, Kevin Petrecca, Michael A. Grotzer, Lyndsey Emery, Jennifer A. Chan, Luca Massimi, Elizabeth Vera-Bolanos, Antonio Omuro, Richard Everson, Stewart Goldman, Sarah Leary, Alvaro Lassaletta, Sofia Nunes, Ralph P. Ermoian, Betty Luu, Cynthia Hawkins, Amulya A. Nageswara Rao, Jeffrey R. Leonard, Maura Massimino, Teresa Tuñón, Massimo Zollo, James M. Olson, Almos Klekner, Andrey Korshunov, Ute Bartels, Tong Lin, Roger J. Packer, Matthias A. Karajannis, David W. Ellison, Christopher Dunham, David D. Eisenstat, Jaume Mora, Martin Mynarek, Erwin G. Van Meir, Roger E. McLendon, Karel Zitterbart, Corrine Gardner, Giuseppe Cinalli, Amar Gajjar, Kenneth Aldape, Karin M. Muraszko, Vijay Ramaswamy, Thomas Hielscher, Ronald L. Hamilton, Lola B. Chambless, Michael D. Prados, David T.W. Jones, Harshad Ladha, Horacio Soto, Wiesława Grajkowska, Jason E. Cain, Felice Giangaspero, Marcel Kool, Eric S. Lipp, William H. Yong, Andrew J. Grossbach, Tibor Hortobágyi, Tarek Shalaby, Helen Wheeler, Peter Hauser, Marie Lise C. van Veelen, Kristian W. Pajtler, Dorcas Fulton, Mariarita Santi, László Bognár, Jaroslav Sterba, Jing Wu, Ji Yeoun Lee, Carlos Gilberto Carlotti, Katja von Hoff, Stefan Rutkowski, Michael D. Taylor, Daniela Pretti da Cunha Tirapelli, Phillipe Metellus, Stephen C. Mack, Thomas E. Merchant, Samer K. Elbabaa, Marc Remke, Girish Dhall, Riccardo Soffietti, Eric Bouffet, Miguel A. Guzman, Khalida Wani, Charles G. Eberhart, Terri S. Armstrong, Tom Mikkelsen, Francesca R. Buttarelli, Nada Jabado, Paul G. Fisher, Juliette Hukin, Maryam Fouladi, Sama Ahsan, Sueli Mieko Oba-Shinjo, Linda M. Liau, Satoru Osuka, Sridharan Gururangan, Peter B. Dirks, Eugene Hwang, Howard Colman, H. Ian Robins, Caterina Giannini, Suely Kazue Nagahashi Marie, Frank van Landeghem, Mark R. Gilbert, Ulrich Schüller, Florence M.G. Cavalli, David Zagzag, Ian F. Pollack, Claudia C. Faria, Stefan M. Pfister, Shin Jung, Ramaswamy, V, Hielscher, T, Mack, Sc, Lassaletta, A, Lin, T, Pajtler, Kw, Jones, Dt, Luu, B, Cavalli, Fm, Aldape, K, Remke, M, Mynarek, M, Rutkowski, S, Gururangan, S, Mclendon, Re, Lipp, E, Dunham, C, Hukin, J, Eisenstat, Dd, Fulton, D, van Landeghem, Fk, Santi, M, van Veelen, Ml, Van Meir, Eg, Osuka, S, Fan, X, Muraszko, Km, Tirapelli, Dp, Oba Shinjo, Sm, Marie, Sk, Carlotti, Cg, Lee, Jy, Rao, Aa, Giannini, C, Faria, Cc, Nunes, S, Mora, J, Hamilton, Rl, Hauser, P, Jabado, N, Petrecca, K, Jung, S, Massimi, L, Zollo, Massimo, Cinalli, G, Bognár, L, Klekner, A, Hortobágyi, T, Leary, S, Ermoian, Rp, Olson, Jm, Leonard, Jr, Gardner, C, Grajkowska, Wa, Chambless, Lb, Cain, J, Eberhart, Cg, Ahsan, S, Massimino, M, Giangaspero, F, Buttarelli, Fr, Packer, Rj, Emery, L, Yong, Wh, Soto, H, Liau, Lm, Everson, R, Grossbach, A, Shalaby, T, Grotzer, M, Karajannis, Ma, Zagzag, D, Wheeler, H, von Hoff, K, Alonso, Mm, Tuñon, T, Schüller, U, Zitterbart, K, Sterba, J, Chan, Ja, Guzman, M, Elbabaa, Sk, Colman, H, Dhall, G, Fisher, Pg, Fouladi, M, Gajjar, A, Goldman, S, Hwang, E, Kool, M, Ladha, H, Vera Bolanos, E, Wani, K, Lieberman, F, Mikkelsen, T, Omuro, Am, Pollack, If, Prados, M, Robins, Hi, Soffietti, R, Wu, J, Metellus, P, Tabori, U, Bartels, U, Bouffet, E, Hawkins, Ce, Rutka, Jt, Dirks, P, Pfister, Sm, Merchant, Te, Gilbert, Mr, Armstrong, T, Korshunov, A, Ellison, Dw, Taylor, M. d., Ramaswamy V., Hielscher T., Mack S.C., Lassaletta A., Lin T., Pajtler K.W., Jones D.T.W., Luu B., Cavalli F.M.G., Aldape K., Remke M., Mynarek M., Rutkowski S., Gururangan S., McLendon R.E., Lipp E.S., Dunham C., Hukin J., Eisenstat D.D., Fulton D., Van Landeghem F.K.H., Santi M., Van Veelen M.-L.C., Van Meir E.G., Osuka S., Fan X., Muraszko K.M., Tirapelli D.P.C., Oba-Shinjo S.M., Marie S.K.N., Carlotti C.G., Lee J.Y., Rao A.A.N., Giannini C., Faria C.C., Nunes S., Mora J., Hamilton R.L., Hauser P., Jabado N., Petrecca K., Jung S., Massimi L., Zollo M., Cinalli G., Bognar L., Klekner A., Hortobagyi T., Leary S., Ermoian R.P., Olson J.M., Leonard J.R., Gardner C., Grajkowska W.A., Chambless L.B., Cain J., Eberhart C.G., Ahsan S., Massimino M., Giangaspero F., Buttarelli F.R., Packer R.J., Emery L., Yong W.H., Soto H., Liau L.M., Everson R., Grossbach A., Shalaby T., Grotzer M., Karajannis M.A., Zagzag D., Wheeler H., Von Hoff K., Alonso M.M., Tunon T., Schuller U., Zitterbart K., Sterba J., Chan J.A., Guzman M., Elbabaa S.K., Colman H., Dhall G., Fisher P.G., Fouladi M., Gajjar A., Goldman S., Hwang E., Kool M., Ladha H., Vera-Bolanos E., Wani K., Lieberman F., Mikkelsen T., Omuro A.M., Pollack I.F., Prados M., Robins H.I., Soffietti R., Wu J., Metellus P., Tabori U., Bartels U., Bouffet E., Hawkins C.E., Rutka J.T., Dirks P., Pfister S.M., Merchant T.E., Gilbert M.R., Armstrong T.S., Korshunov A., Ellison D.W., Taylor M.D., and Neurosurgery
- Subjects
Male ,Ependymoma ,Cancer Research ,medicine.medical_treatment ,cancer research ,oncology ,posterior fossa ependymoma ,cytoreductive surgery ,radiation therapy ,Infratentorial Neoplasms ,Cohort Studies ,0302 clinical medicine ,Retrospective Studie ,Medicine ,Pediatric ependymoma ,Child ,10. No inequality ,Infratentorial Neoplasm ,biology ,Cytoreduction Surgical Procedures ,Combined Modality Therapy ,3. Good health ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Female ,Radiology ,Human ,Adult ,medicine.medical_specialty ,Adolescent ,Fossa ,Ependymoma, biomarkers ,03 medical and health sciences ,Original Reports ,Humans ,Retrospective Studies ,Chemotherapy ,business.industry ,Proportional hazards model ,Infant ,Retrospective cohort study ,biology.organism_classification ,medicine.disease ,Surgery ,Radiation therapy ,Cohort Studie ,business ,030217 neurology & neurosurgery - Abstract
Purpose Posterior fossa ependymoma comprises two distinct molecular variants termed EPN_PFA and EPN_PFB that have a distinct biology and natural history. The therapeutic value of cytoreductive surgery and radiation therapy for posterior fossa ependymoma after accounting for molecular subgroup is not known. Methods Four independent nonoverlapping retrospective cohorts of posterior fossa ependymomas (n = 820) were profiled using genome-wide methylation arrays. Risk stratification models were designed based on known clinical and newly described molecular biomarkers identified by multivariable Cox proportional hazards analyses. Results Molecular subgroup is a powerful independent predictor of outcome even when accounting for age or treatment regimen. Incompletely resected EPN_PFA ependymomas have a dismal prognosis, with a 5-year progression-free survival ranging from 26.1% to 56.8% across all four cohorts. Although first-line (adjuvant) radiation is clearly beneficial for completely resected EPN_PFA, a substantial proportion of patients with EPN_PFB can be cured with surgery alone, and patients with relapsed EPN_PFB can often be treated successfully with delayed external-beam irradiation. Conclusion The most impactful biomarker for posterior fossa ependymoma is molecular subgroup affiliation, independent of other demographic or treatment variables. However, both EPN_PFA and EPN_PFB still benefit from increased extent of resection, with the survival rates being particularly poor for subtotally resected EPN_PFA, even with adjuvant radiation therapy. Patients with EPN_PFB who undergo gross total resection are at lower risk for relapse and should be considered for inclusion in a randomized clinical trial of observation alone with radiation reserved for those who experience recurrence.
- Published
- 2016